HIV-1 infection MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Doravirine (Pifeltro)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DORAVIRINE
Current Sponsor code: MK-1439
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is HIV-1 positive with plasma HIV-1 RNA = 500 copies/mL at the Screening Visit and confirmed upon repeat testing (Visit 2 [or Visit 3 if required]) during the Run-in Period. In addition, the log change in HIV-1 RNA must meet 1 of the following criteria at a confirmation visit: - =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Has HIV-2 infection. 2. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 3. Has HBV co-infection (defined as HBsAg-positive or HBV DNA positive) and is not currently being treated for HBV. 4. Has a history or current evidence of any condition (including active TB co-infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration. 5. Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period. 6. Is taking DOR as part of his/her current failing antiretroviral regimen. 7. Is taking EFV, etravirine, or nevirapine. 8. Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period. 9. Has exclusionary laboratory values at the Screening Visit 10. Is female and is expecting to conceive or donate eggs at any time during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To evaluate the antiretroviral activity of doravirine/islatravir (DOR/ISL) compared to placebo, each given in combination with failing antiretroviral therapy (ART) as assessed by the percentage of participants achieving =0.5 log10 decrease in HIV-1 RNA from study baseline (Day 1) to Day 8 (Part 1) 2.2. To evaluate the safety and tolerability of DOR/ISL as assessed by review of the accumulated safety data through Week 25 and Week 49. ;Secondary Objective: 1.To evaluate the safety and tolerability of DOR/ISL through Week 97 2.To assess antiretroviral activity of DOR, ISL+failing antiretroviral therapy (ART) based on % of participants with =0.5 and =1.0 log10 decrease in HIV-1 RNA 3.To assess antiretroviral activity of DOR, ISL + failing ART based on % of participants with =0.5 log10 decrease in HIV-1 RNA; mean change in HIV-1 RNA; and % of participants with =1.0 log10 decrease in HIV-1 RNA 4.To assess antiretroviral activity of DOR, ISL, optimized background therapy (OBT) based on % of participants achieving =0.5 log10 and =1.0 log10 decrease in HIV-1 RNA; mean change in HIV-1 RNA; % of participants with HIV-1 RNA <50 and <200 copies/mL; and % of participants with HIV-1 RNA <40 copies/mL 5.To assess development of viral drug resistance to DOR, ISL, OBT 6.To assess the role of baseline antiviral resistance on virologic outcomes 7.To assess the change in CD4+ T-cell counts ;Primary end point(s): 1. Percentage of participants receiving DOR/ISL with =0.5 log10 decrease from baseline in HIV-1 RNA compared to placebo treatment 2. Percentage of participants with =1 adverse events (AEs) 3. Percentage of participants withdrawing from study treatment due to AE(s) ;Timepoint(s) of evaluation of this end point: 1. Day 1 (baseline) to Day 8 2. Up to 49 weeks 3. Up to 49 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1.Up to 97 wks 2.Up to 97 wks 3.D 1(BL) to D 8 4.D 1(BL) to D 8 5.D 1(BL) to D 8 6.D 1(BL) to D 8 7.D 1(BL) to D 8 8.D 1(BL) to D 8 9.D 8(BL) to W 25 10.D 1(BL) to W 49 11.D 1(BL) to W 97 12.D 8(BL) to W 25 13.D 1(BL) to W 49 14.D 1(BL) to W 97 15.D 8(BL) to W 25 16.D 1(BL) to W 49 17.D 1(BL) to W 97 18.D 8(BL) to W 25 19.D 1(BL) to W 49 20.D 1(BL) to W 97 21.D 8(BL) to W 25 22.D 1(BL) to W 49 23.D 1(BL) to W 97 24.D 8(BL) to W 25 25.D 1(BL) to W 49 26.D 1(BL) to W 97 27.W 25 28.W 49 29.W 25 30.W 49 31.W 25 32.W 49 33.D 1(BL) to W 25 34.D 1(BL) to W 49 35.D 1(BL) to W 97 36.D 1(BL) to W 25 37.D 1(BL) to W 49 38.D 1(BL) to W 97 39.D 1(BL) to W 25 40.D 1(BL) to W 49 41.D 1(BL) to W 97 42.D 8(BL) to W 25 43.D 8(BL) to W 49 44.D 8(BL) to W 97;Secondary end point(s): 1.Percentage of participants with =1 adverse events (AEs) 2.Percentage of participants withdrawing from study therapy due to AEs 3.Percentage of participants receiving DOR or ISL (given with ART) with=0.5 log10 decrease in HIV-1 RNA compared to placebo treatment 4.Mean change from baseline in HIV-1 RNA following treatment with DOR/ISL (given with ART) , DOR, or ISL compared to placebo treatment 5.Percentage of participants receiving DOR/ISL (given with ART), DOR, or ISL with =1.0 log10 decrease from baseline in HIV-1 RNA compared to placebo treatment 6.Percentage of participants receiving DOR/ISL (given with ART) with = 0.5 log10 decrease from baseline in HIV-1 RNA compared to DOR or ISL treatment 7.Mean change from baseline in HIV-1 RNA following treatment with DOR/ISL (given with ART) compared to DOR or ISL treatment 8.Percentage of participants receiving DOR/ISL (given with ART) with =1.0 log10 decrease from baseline in HIV-1 RNA compared to DOR or ISL treatment 9.Percentage of participants receiving DOR/ISL (given with ART) + OBT with =0.5 log10 decrease from baseline in HIV-1 RNA compared to DOR or ISL treatment 10.Percentage of participants receiving DOR/IS | — |
Countries
Australia, Canada, Chile, Colombia, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Peru, Portugal, Russian Federation, South Africa, Spain, Ukraine, United Kingdom, United States
Outcome results
None listed